In conventional solid-phase synthesizers, particularly multiple synthesizers wherein a single needle is used for all of a number of reaction vessels, repeated reaction tends to cause incomplete reaction, cross contamination, increased frequency in moving of the needle, and the like. This problem arises due to the different reactivities of individual chemical derivatives in the case of multiple reactions. In addition, from the viewpoint of efficiency-related factors, such as yield and purity of reaction product, it is disadvantageous to carry out all reactions by the same method or under the same conditions. Moreover, the single needle must be frequently moved reciprocally among a large number of reaction vessels, various reagent containers and washing ports, which results in increased operating time or side reactions. Specifically, when a single needle is used with a number of reaction vessels, while the needle is acting on one reaction vessel, the other reaction vessels must wait, and in addition, washing must be completed by the reach of the needle to another reaction vessel, which results in an increase in time required for each reaction. This method is also disadvantageous from the viewpoint of the mechanical strength and durability of the apparatus, because it involves a large number of movements. Moreover, when a needle contacts with resin by bubbling or stirring in the reaction vessel, the resin attaches to the needle, thereby causing loss of resin and cross contamination.
In the apparatus wherein the reagents in respective reaction vessels are aspirated and discharged on a one-by-one basis by a needle, not only the discharge of the reagents, washing solvents, etc. is incomplete, but also thorough washing is essential for each discharge, which results in cross contamination.
In the apparatus wherein the reagents are simultaneously discharged from all reaction vessels under reduced pressure with the bottom portion thereof kept at a negative pressure, there are some difficult problems in the maintenance of tightness between the vessels and the bottom portion containers and in uniform discharge due to the differences in the properties of reaction products among the items.
Also, in conventional methods, it must be outside the reaction apparatus to take out the reaction product from the solid phase by another deprotecting reaction, namely cleavage, after reaction, i.e., they are not efficient solid-phase synthesizing methods.